For over a century, food scientists have been on a quest to satisfy the world’s sweet tooth without the associated health risks of sugar consumption. From early artificial sweeteners to modern plant-based alternatives, the goal has remained consistent: to provide sweetness without the excess calories, tooth decay, or increased risks of obesity and diabetes.
Researchers at Tufts University have now reported a significant breakthrough in this pursuit. In a study published in Cell Reports Physical Science, a team led by Nik Nair, an associate professor of chemical and biological engineering, has unveiled a novel biological method to produce tagatose, a rare sugar that mirrors the taste of table sugar but with fewer health drawbacks.
Tagatose is naturally found in minute quantities in certain dairy products and fruits like apples and oranges. However, its concentration is typically less than 0.2% of natural sugars, making extraction from food impractical. Consequently, tagatose has traditionally been manufactured through costly and inefficient processes.
Why Tagatose Matters
Tagatose is approximately 92% as sweet as sucrose and contains about one-third of the calories. It has been granted “generally recognized as safe” status by the U.S. Food and Drug Administration, placing it in the same category as common ingredients like salt and baking soda.
Unlike table sugar, tagatose is only partially absorbed in the small intestine, with much of it reaching the colon where it is fermented by gut bacteria. This results in only minor increases in blood glucose and insulin levels. Clinical studies have demonstrated very low spikes in these metrics following tagatose consumption.
Furthermore, tagatose behaves similarly to sugar in culinary applications, providing bulk, browning during heating, and closely matching sugar’s taste and texture. This makes it an attractive option for food manufacturers seeking to reduce sugar content without resorting to high-intensity sweeteners that lack volume.
Nonetheless, production constraints have limited its widespread use. Traditional methods often begin with galactose, derived from lactose in milk, where only half of the lactose can be utilized in tagatose production, resulting in inherent waste. Other methods starting from fructose often stall before converting the majority of the sugar.
Rewriting Biology Inside Bacteria
“Our research team aimed to solve that problem by starting with glucose, one of the cheapest and most abundant sugars available. To do that, we turned to a natural sugar-processing route in Escherichia coli called the Leloir pathway. This pathway normally breaks down galactose into glucose for energy,” Nair explained to The Brighter Side of News.
“The challenge was to run it backward,” he continued.
To facilitate this reversal, the researchers sought a specific enzyme. After testing several candidates, they identified one from a slime mold, Dictyostelium discoideum. This enzyme, known as galactose-1-phosphate-selective phosphatase or Gal1P, removes a phosphate group from a galactose-linked molecule.
The enzyme’s precision was noteworthy. Despite the slight differences between galactose and glucose, this enzyme displayed a strong preference for galactose-related compounds. This selectivity enabled the pathway to reverse, converting glucose into galactose within the cell.
“The key innovation in the biosynthesis of tagatose was in finding the slime mold Gal1P enzyme and splicing it into our production bacteria,” Nair stated.
Once galactose was formed, a second enzyme called arabinose isomerase converted part of it into tagatose.
What the Bacteria Produced
Initial tests revealed promising results. When fed galactose, the engineered bacteria produced more tagatose than unmodified strains. The real test, however, was with glucose. Ordinary strains showed no tagatose production. After additional genetic modifications that prevented glucose from being used for normal energy processes, the bacteria began channeling it into the new pathway.
From 30 grams per liter of glucose, the system produced up to 8.7 grams per liter of galactose and about 1.4 grams per liter of tagatose. These results were achieved without extensive optimization.
The team also discovered that increasing the production of the slime mold enzyme enhanced both galactose and tagatose levels, underscoring its pivotal role. The pathway’s theoretical yield could reach nearly 95%, significantly surpassing traditional manufacturing methods that achieve between 40% and 77%. Although some sugar still supports cell growth, the efficiency remains impressive.
Pushing the Balance Toward Tagatose
One limitation persists: the bacteria produce more galactose than tagatose. This reflects the natural balance of the galactose-to-tagatose step. To address this, the researchers experimented with several strategies.
Higher temperatures were found to favor tagatose formation, although excessive heat proved lethal to the cells. Moderate heat was beneficial without halting the system. The team also modified sugar transport across the cell membrane. By removing certain transport genes, more galactose was retained inside, increasing tagatose output by up to 1.66 times.
These findings indicate clear paths for future enhancement, including fine-tuning temperature, transport, and feeding conditions. The research findings are available online in the journal Cell Reports Physical Science.
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